|Intimacy Level:|| Former rivals|
The two perform The Boy Is Mine together, after Mercedes starts dating Puck, who Santana used to date. The song turns into a physical confrontation, and also becomes very verbal towards each other. Mr. Schue breaks them up, but Santana goes for another shove after this. At the end, Santana tells Mercedes that Puck's hair is growing back, meaning he will break up with Mercedes after it does.River Deep, Mountain High. The two seem friendly after the performance, and Santana tells the club they've already made custom bibs for Breadstix. When Sam and Quinn are announced the winners of the Duets Contest, Santana gets angry and tries to get up and hurt Quinn but, Mercedes stops her. Santana starts to cry and Mercedes rubs her head and says "It Okay,It's Okay." Dancing Queen at the Prom and seem to be on good terms. At first, they look sad and worried for Kurt, but then both are having fun and dancing around with each other while they sing the song, arm in arm.
Despite the fact that the two seemed to have become friends, Mercedes approves of Will's decision to suspend Santana from the Glee club (due to her and the Cheerios setting a purple piano on fire, on Sue's orders), noting that it's about time people took the club seriously if they are going to succeed at Nationals this year.
The Troubletones performs the Survivor/I Will Survive at Sectionals. Mercedes and Santana lead the song.
Santana and Mercedes sing The First Time Ever I Saw Your Face along with Rachel and Tina where they have flashbacks. Santana has a flashback to the first time she met Brittany and Mercedes has a flashback to the first time she met Sam. Once the song ends Mercedes leaves the auditorium in tears and goes to the restroom. Santana follows Tina and Rachel to the restroom to comfort Mercedes and to see what is upsetting her. Mercedes tearfully confesses to them that it wasn't Shane, but Sam, that she thought of during the song. Santana looks sympathetic towards her, and a little concerned.
Will is worried about both their futures, since he's aware that neither of them have any plans yet. They are thus both made finalists in the dance-competition and rewarded with an assignment to cover a song from "Saturday Night Fever." Santana along with Brittany helps Mercedes by singing back-up for her during Disco Inferno.
Mercedes and Santana, along with Brittany, Sugar, and Tina are all involved in the abusive joke made towards Coach Beiste and her black eye. Sue, Roz, and Shannon inform the girls that their assignment is to perform a song that was about female empowerment. Together, they perform Cell Block Tango, which is received negatively by them. Later, when Coach Beiste is honest to the group about the abuse she went through, they perform Shake It Out with Tina.
Near the beginning, Santana and Mercedes are seen fooling around and laughing together in the background. When Will congratulated the nominees for Prom King and Queen, Mercedes was seen giving Santana a high-five. They and the other New Directions members sing and enjoy themselves at prom.
Together with Brittany they approach Coach Beiste after learning that she is still in a relationship with Cooter Menkins.
When Mercedes falls ill, Santana is seen taking care of her.
During the last week of their time at school, Mercedes, Sam and Santana discuss Mercedes' future plans. Santana congratulates her for being able to move to Los Angeles, as she dreamed, and hugs her. Santana admits that if it weren't Mercedes, she'd be terribly jealous of her, implying a deep friendship between the two of them.
Santana and Mercedes reunite with Finn, Puck, Quinn, and Mike. Together they sing Homeward Bound/Home, in the school auditorium. Later, the six of them go to Breadstix and discuss their lives after graduation and Kurt and Rachel's absence. Later, Finn asks them to mentor the newbies of New Directions. Santana happens to mentor Marley and Mercedes happens to mentor Unique, and Marley and Unique are best friends.
Sang Together (In a Group Number)
- Cherish/Cherish by Madonna/The Association. (Heart)
- Disco Inferno by The Trammps. (Saturday Night Glee-ver)
- Both have dated Puck and Sam.
- Both were frenemies with Rachel. As of now, they are both friends with her.
- Their dads work in similar professions, Santana's dad is a doctor and Mercedes' is a dentist. (Throwdown, Britney/Brittany, Saturday Night Glee-ver)
- They were the leads in The Troubletones.
- Santana sometimes puts weird things in Mercedes' food. (Duets)
- They both have mentored Marley at one point in Season Four (Santana in Thanksgiving, and Mercedes in Wonder-ful).
- According to Santana, they have the best voices in the Glee Club. (Duets)